Biplab Kumar Das

Design and synthesis of N-nonpolar nucleobase dipeptides: application of the Ugi reaction for the preparation of dipeptides having fluoroarylalkyl groups appended to the nitrogen atom

A single-step one-pot synthesis based on the Ugi four-component condensation of previously unknown dipeptides, 2, 3, 4 and 5, having a fluoroaromatic group appended to the nitrogen atom, is described. The series of dipeptides produced here can be viewed as nonpolar nucleobase dipeptides since the difluorotoluene nucleoside 1 is a well known nonpolar analogue of natural thymidine. A mixture of N-protected amino acids 7, fluorophenethylamines 6, isocyanides 8, and acetone or paraformaldehyde are stirred in methanol in the presence of 3 A molecular sieves to furnish the N-fluoroarylethyl-Aib- or -Gly-containing dipeptides 2 or 3, in moderate yields. The dipeptides 2d and 3b, having a cyclohex-1-enamide moiety, are deprotected readily with 3 M HCl in THF to afford the free dipeptides in high yields. The N-fluoroarylmethyl-Aib- or -Gly-containing β-alanyl dipeptides 4 or 5, designed based on the structure of 2′,5′-linked isoDNA, are also synthesized in a similar fashion to the preparation of 2, in moderate to good yields as both protected and free dipeptides.

Analgesic, anti-inflammatory, and anti-oxidant activities of Phlogacanthus thyrsiflorus leaves.

Abstract Background: Our present study was carried out to explore the potential role of the methanol extract from the leaves of Phlogocanthus thyrsiflorus (PT) Nees. in central and peripheral analgesic activities using hot plate and acetic acid-induced writhing methods. We also tested the anti-inflammatory effects and anti-oxidant activity using carrageenan-induced paw edema and the DPPH method, respectively. Methods: Methanol extracts of PT leaves were prepared using 500 g powder in 1.8 L methanol by percolation method, followed by evaporation in a rotary evaporator under controlled temperature and pressure. The crude methanol extract was dried by freeze drier and preserved at 4 °C. Results: Oral administration of PT significantly (p<0.05) increased the reaction time at 55.73% (250 mg/kg) and 72.81% (500 mg/kg) inhibition (p<0.05) in the hot plate test at 3 h. PT significantly (p<0.05) inhibited 42.17% (250 mg/kg) and 56.63% (500 mg/kg) acetic acid-induced writhing. PT leaves (250 and 500 mg/kg) also significantly (p<0.05) inhibited paw edema 6 h after carrageenan injection. Furthermore, this plant showed significant (p<0.05) free radical-scavenging activity at a dose range of 25–800 μg/mL. Conclusions: Based on the findings, we can conclude that PT leaf possesses analgesic, anti-inflammatory, and anti-oxidant activities. Preliminary phytochemical study of PT leaves revealed the presence of flavonoids, tannins and triterpens in methanol extract which could be correlated with its observed biological activities.

Antinociceptive and anti-inflammatory activity of the bark extract of Plumeria rubra on laboratory animals.

No. 3O-03. 3. B. Das, S. Nakamura, N. Shibata, T. Toru, “Synthesis, Spectroscopic and Photodynamic Properties of Fluorinated Phthalocyanines,” 33 Fluorine Conference of Japan, Hachioji, Japan, October 2009, Abstract No. P-28. 4. B. Das, S. Nakamura, M. Tanaka, T. Sasaki, N. Shibata, T. Toru, “Novel Amphiphilic Deoxyribonucleosides Appended Perfluoroalkylated Phthalocyanines: Synthesis, Photophysical and Photodynamic Properties,” 55 Annual Meeting of The Pharmaceutical Society of Japan in Tokai Branch, Nagoya, Japan, July 2009, Abstract No. B-11. 5. B. Das, S. Nakamura, N. Shibata, T. Toru, “Design, Synthesis, Photophysical and Photodynamic Properties of Perfluoroalkylated Phthalocyanines Conjugated with Deoxyribonucleosides,” International Conference on Fluorine Chemistry, Kyoto, Japan, May 2009, Abstract No. P-34. 6. B. Das, H. Yoshiyama, S. Nakamura, N. Shibata, T. Toru, “1,3-Butadiyne Linked Perfluoroalkylated Phthalocyanine Dyads: Synthesis, Photophysical and Electrochemical Properties,” The 89 Annual Meeting of The Chemical Society of Japan, Tokyo, Japan, March 2009, Abstract No. 1K2-05. 7. B. Das, N. Shibata, S. Nakamura, T. Toru, “Perfluoroalkylated Phthalocyanines Conjugated with Deoxyribonucleic Acids: Synthesis and Properties,” 32 Fluorine Conference of Japan, Nagoya, Japan, November 2008, Abstract No. P-21. 8. B. Das, N. Shibata, S. Nakamura, T. Toru, “Design, Synthesis and Photophysical Properties of Perfluoroalkylated Phthalocyanines Conjugated with Deoxyribonucleic Acids,” 39 Annual Meeting of Union of Chemistry-Related Societies in Chubu Area, Nagoya, Japan, November 2008, Abstract No. 1Y-09.

Synthesis of nonpolar peptide nucleic acid monomers containing fluoroaromatics

A general strategy for the synthesis of nonpolar peptide nucleic acid monomers containing fluoroaromatics (F-PNA) is described. These compounds have been designed as hybrid analogues of the difluorotoluene nucleoside, F (1) with PNA. Fluorophenylacetic acid derivatives 9 were coupled to the Boc-protected pseudopeptide backbone 8 by a standard peptide coupling reaction using DhbtOH and DCC in the presence of triethylamine to afford the doubly protected F-PNA monomers 14 in moderate to good yields. The ethyl esters 14a, 14c and 14e underwent hydrolytic cleavage under basic conditions to generate N-protected F-PNA monomers 15 in good yields. The tert-butyl esters 14b, 14d were treated with TFA in dichloromethane to produce the free F-PNA monomers 16 in good to excellent yields. The β-F-PNA monomers designed based on the structure of 2′,5′-linked isoDNA were also synthesized in a similar fashion to the preparation of F-PNA monomers in moderate to good yields as both N-protected and free monomers.

Analgesic, anti-inflammatory and antipyretic effects of Ixora coccinea

Abstract Background: The present study was carried out to explore the potential of the ethanol extract of Ixora coccinea L. (IC) leaves as analgesic, anti-inflammatory and antipyretic agents using the hot-plate, acetic acid-induced writhing, carrageenan-induced paw edema and brewer’s yeast-induced pyrexia tests in rodents. Methods: The extract was prepared by soaking the dried powdered leaves of IC in ethanol for 2 days. The filtrate thus obtained by filtration and evaporation was considered as a stock solution and was used in all experimental models. Results: Oral administration of IC (250 and 500 mg/kg) significantly (p<0.05) increased the reaction time in the hot-plate test. Ixora coccinea (250 and 500 mg/kg) produced 56.14% and 63.16% inhibition (p<0.05) in acetic acid-induced writhing. It also (250 and 500 mg/kg) produced significant (p<0.05) inhibition of paw edema pronounced at 6 h after carrageenan injection. Intraperitoneal administration of IC (250 and 500 mg/kg) lowered the body temperature in brewer’s yeast-induced hyperthermia. Conclusions: Based on the findings, it may be concluded that the IC leaves possessed analgesic, anti-inflammatory, and antipyretic activities. Phytochemical constituents of IC leaves such as flavonoids, tannins, and triterpenes in ethanol extract could be correlated with its observed biological activities.

Analgesic and Anti-inflammatory Activities of the Fruit Extract of Ampelocissus latifolia (Roxb) on Laboratory Animals

Aim of Study: This study was aimed to evaluate the possible analgesic and antiinflammatory properties of the ethanol extract of fruit of Ampelocissus latifolia (Roxb). Study Design: Assessment of analgesic and anti-inflammatory activities. Place and Duration of Study: Department of Pharmacy, North South University, Dhaka, Bangladesh, between June 2012 and March 2013. Methodology: The crude ethanol extract was investigated for the anti-inflammatory effect on Long Evans rats using carrageenan induced rat paw edema method. For antiinflammatory study, 20 rats were divided into 4 different groups, each receiving either distilled water, standard drug or the extract at the doses of 250 and 500mg/kg body weight (BW). The analgesic activity was evaluated by hot plate and acetic acid induced writhing method in Swiss albino mice divided into 4 different groups (control, standard and extract at two different doses of 250 and 500 mg/kg BW). Original Research Article British Journal of Pharmaceutical Research, 4(12): 1477-1485, 2014 1478 Results: The results of preliminary phytochemical study revealed the presence of alkaloids, flavonoids, tannins, glycosides in significant amounts. The results of anti inflammatory activity study showed that the fruit extracts at a dose of 250 mg/kg and 500 mg/kg inhibited carrageenan-induced paw edema in LongEvans rats. Both the extracts were able to show a dose dependent anti-inflammatory activity as compared to diclofenac sodium used as a standard drug. The extract elicited a highly significant (p<0.001) analgesic activity in a dose dependent manner on hot plate method, acetic acid-induced writhing test. In the hot plate method, the extract increased the reaction time of heat sensation to 94.71% and 82.7% at the doses of 250 and 500 mg/kg BW while that of the standard drug was 61.45% at the 3 rd hour of study. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 50.57% and 59.77% at 250 and 500 mg/kg doses respectively (p<0.001). Conclusion: The anti-inflammatory and analgesic effect of the ethanol fruit extract of Ampelocissus latifolia (Roxb) may be due to the presence of various chemical constituents especially flavonoids, tannins, alkaloids or terpenoids. These experimental findings would further establish the scientific basis of the traditional uses of the plant in the management of inflammatory conditions as well as control of pain.

Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum.

We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract. The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-induced writhing and formalin test. The ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed significant (P<0.05) analgesic effect in all test methods (hot plate, acetic acid-induced writhing and formalin). The analgesic activity was compared with a standard drug (ketorolac at 10 mg/kg). Based on the present findings and previous literature review it can be concluded that flavonoids and tannins might be responsible for the analgesic activity. We suggest that ethanol extract of Oroxylum indicum might have potential chemical constituents that could be used in the future for the development of novel analgesic agent.

Application of the Ugi four-component condensation reaction for the synthesis of α,α- and α,β-dipeptides substituted with fluoroarylalkyl pendent groups

We report a single step synthesis based on the Ugi four-component condensation of previously unknown α,α- and α,β-dipeptides, 2 and 8, having fluoroaromatic groups appended to the nitrogen atom.